Asialoglycoprotein receptor (ASGPR) is an endocytotic cell surface receptor only expressed by mammal hepatocytes, specifically recognizing the saccharide chain with terminal galactose residues or terminal N-Acetylgalactosamine (GaINAc) residues. SPECT image of liver ASGPR is obviously better than other imaging methods and has a higher affinity and a rapid absorption for liver. When hepatopathy, the amount of ASGPR may change. According to such a property, glycopeptides or glycoproteins having galactose or GaINAc residues can be developed as liver-receptor imaging agents.
Applicability of liver-receptor imaging agents is as follows:
1. Patents suffering the liver transplantation usually have transient anoxia. Whether liver transplanting surgery succeeds will be immediately known by liver-receptor imaging after transplanting the liver.
2. Liver-receptor imaging is evidence for the real liver function. After Glycopeptides or glycoproteins having galactose residues or GaINAc residues bind to ASGPR, they may enter into liver cells by receptor-mediated endocytosis. When hepatopathy, liver cells may reduce and imaging value may lower. Therefore, the amount of the real liver function may be evaluated.
These liver-receptor imaging agents have potential for quantifying liver storage ability, and thus imaging absorption of these liver-receptor imaging agents can use to evaluate severity for the course of liver disease.
Indium-111 (In-111 or 111In) has some advantages for commonly applying in nuclear medicine, including:
(1) A suitable physical half-life (about 67 hours), and thus there being enough tome for observing the metabolic change of radiopharmaceuticals in human bodies.
(2) A very short biological half-life.
(3) A common nuclide of hospitals for easy access. Most In-111 radiopharmaceuticals, which can add In-111 in anytime to dispense for labeling, is convenient to healthcare centers and users, and thereby improve flexibility and supply reliability for usage of In-111 radiopharmaceuticals in the nuclear medicine department.
(4) Gamma-ray released from In-111 have suitable energy of about 171 key and can apply to all gamma-imaging equipment.
(5) In-111 production of Taiwanese research institute ((The Institute of Nuclear Energy Research (INER)) have been for several years, and have a well and stable quality. Thus, the said In-111 can offer hospitals and research institutions in a cheaper price to produce In-111 radiopharmaceuticals and have competitive advantages in the market.
Traditional Tc-99m-DTPA-Galactosyl-Albumin (Tc-99m DTPA-GSA) is known as a liver-receptor imaging injection which Albumin was as a backbone to connect unanticipated amount of galactosamine and diethylene triamine pentaacetic acid (DTPA). It fails to control this process to ensure that the mount of connected DTPA per batch is the same, so there will be a great difference in radiochemical specific activity of labeled Tc-99m per batch. To ensure constant radiochemical specific activity and remain imaging quality of high reproducibility, it is necessary to develop a new backbone for connecting a fixed amount of galactosamine and DTPA.
Tyrosine-glutamic acid-glutamic acid (YEE), tyrosine-Aspartic acid-Aspartic acid (YDD) and tyrosine-glutamic acid-glutamic acid-glutamic acid (YEEE) use peptides such as glutamyl-glutamic acid (EE) aspartyl-aspartic acid (DD) to be a backbone for preparing poly-saccharide chains. YEE and YDD can connect fixed amount of galactosamine and DTPA and be suitable for iodine-labeling, but their development in pharmaceutical industry are limited due to their complicated synthetic steps and low solubility. Further, oxidants such as chloramine T, iodobead, Iodogen or the like should be added when iodine-labeling. If they are used as in vivo image, purification for removing oxidants after the said steps finish is required because these oxidants are toxic for human bodies.
Imaging injections for human should conform to the criteria for labeled products which are germless and have no pyrogen. Autoclave sterilization is the most common method for sterilizing final products at present. This method usually applies in injections to prepare labeled pharmaceuticals in advance for offering hospital use. But if quality of labeled pharmaceuticals after autoclave sterilization has been worse than the before autoclave sterilization one, autoclave sterilization may fail to use in routine need.
Another sterilizing method is by 0.22 μm Membrane Filtration method which labeled products (e.g. the PET tumor imaging agent 18F-FDG) pass through a 0.22 μm Millipore membrane. This method can filtrate bacteria effectively and remain pharmaceutical activity effectively. But standards of pharmaceutical factories should comply with a negative pressure operation, providing a Class 100 (EC GMP Grade A) air environment in virtue of using in radiolabeled products. Thus, a general pharmaceutical factory can not afford such a high Class and the cost thereof.